Introduction

In February 1994, the Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 demonstrated that a three-part regimen of zidovudine (ZDV) could reduce the risk for mother-to-child HIV-1 transmission by nearly 70% (1). The regimen includes oral ZDV initiated at 14-34 weeks' gestation and continued throughout pregnancy, followed by intravenous ZDV during labor and oral administration of ZDV to the infant for 6 weeks after delivery (Table 1). In August 1994, a Public Health Service (PHS) task force issued recommendations for the use of ZDV for reduction of perinatal HIV-1 transmission (2), and in July 1995, PHS issued recommendations for universal prenatal HIV-1 counseling and HIV-1 testing with consent for all pregnant women in the United States (3). Following the results of PACTG 076, epidemiologic studies in the United States and France have demonstrated dramatic decreases in perinatal transmission with incorporation of the PACTG 076 ZDV regimen into general clinical practice (4-9).

Since 1994, advances have been made in the understanding of the pathogenesis of HIV-1 infection and in the treatment and monitoring of HIV-1 disease. The rapidity and magnitude of viral turnover during all stages of HIV-1 infection are greater than previously recognized; plasma virions are estimated to have a mean half-life of only 6 hours (10). Thus, current therapeutic interventions focus on early initiation of aggressive combination antiretroviral regimens to maximally suppress viral replication, preserve immune function, and reduce the development of resistance (11). New, potent antiretroviral drugs that inhibit the protease enzyme of HIV-1 are now available. When a protease inhibitor is used in combination with nucleoside analogue reverse transcriptase inhibitors, plasma HIV-1 RNA levels may be reduced for prolonged periods to levels that are undetectable using current assays. Improved clinical outcome and survival have been observed in adults receiving such regimens (12,13). Additionally, viral load can now be more directly quantified through assays that measure HIV-1 RNA copy number; these assays have provided powerful new tools to assess disease stage, risk for progression, and the effects of therapy. These advances have led to substantial changes in the standard of treatment and monitoring for HIV-1-infected adults in the United States (14). (See the "Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents")

Advances also have been made in the understanding of the pathogenesis of perinatal HIV-1 transmission. Most perinatal transmission likely occurs close to the time of or during childbirth (15). Additional data that demonstrate the short-term safety of the ZDV regimen are now available as a result of follow-up of infants and women enrolled in PACTG 076; however, recent data from studies of animals concerning the potential for transplacental carcinogenicity of ZDV affirm the need for long-term follow-up of children with antiretroviral exposure in utero (16).

These advances have important implications for maternal and fetal health. Healthcare providers considering the use of antiretrovirals in HIV-1-infected women during pregnancy must take into account two separate but related issues: a) antiretroviral treatment of the woman's HIV infection and b) antiretroviral chemoprophylaxis to reduce the risk for perinatal HIV-1 transmission. The benefits of antiretroviral therapy in a pregnant woman must be weighed against the risk for adverse events to the woman, fetus, and newborn. Although ZDV chemoprophylaxis alone has substantially reduced the risk for perinatal transmission, when considering treatment of pregnant women with HIV infection, antiretroviral monotherapy is now considered suboptimal for treatment; combination drug therapy is the current standard of care (14). This report focuses on antiretroviral chemoprophylaxis for the reduction of perinatal HIV transmission and a) reviews the special considerations regarding the use of antiretroviral drugs in pregnant women, b) updates the results of PACTG 076 and related clinical trials and epidemiologic studies, c) discusses the use of HIV-1 RNA assays during pregnancy, d) provides updated recommendations on antiretroviral chemoprophylaxis for reducing perinatal transmission. d) provides updated recommendations on antiretroviral chemoprophylaxis for reducing perinatal transmission, and e) provides recommendations related to use of elective cesarean delivery as an intervention to reduce perinatal transmission.

These recommendations have been developed for use in the United States. Although perinatal HIV-1 transmission occurs worldwide, alternative strategies may be appropriate in other countries. The policies and practices in other countries regarding the use of antiretroviral drugs for reduction of perinatal HIV-1 transmission may differ from the recommendations in this report and will depend on local considerations, including availability and cost of ZDV, access to facilities for safe intravenous infusions among pregnant women during labor, and alternative interventions that may be being evaluated in that area.

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